The present invention relates to a method for preparing porous polyurethane vascular graft prostheses, and in particular to a method for preparing porous polyurethane vascular grafts by placing polyurethane coated mandrel in a coagulant consisting of water, ethanol and optionally aprotic solvent.
Vascular graft prostheses have been used in clinical applications for many years to replace diseased arteries or, to act as shunting for blocked arteries, or to serve as graft fistula for blood dialysis.
Commercial available vascular graft prostheses include woven or knitted polyester fiber (Trademark Dacron) tubes and microporous expanded polytetrafluoroethylene (PTFE, tradename Teflon) tube, such as Gore-Tex(Gore & Associates, Inc.) or Impra Teflon(IMPRA, Inc.) vascular graft prostheses. When vascular graft prostheses made from Dacron or Teflon tubing have a relatively large diameter, good clinical results are obtained because the blood flow rate is high and therefore does not lead to thrombus formation on the luminal surface therein. However, when the Dacron or Teflon tubings have a relatively small diameter, the clinical performance are unsatisfactory because the blood flow rate is usually slow and therefore causes thrombus.
In view of the above mentioned drawbacks to vascular graft prostheses made from Dacron or Teflon, vascular graft prostheses made from polyurethane material have already been developed and have proven to be suitable for this purpose because they possess good blood compatibility.
For example, David Annis, Thien V. How and A. C. Fisher disclose a porous polyurethane vascular graft which is prepared by an electrostatic spinning and winding method. The method includes extruding polyurethane resin "Biomer" (tradename, Ethicon, Inc.) through a spinneret to form filaments and winding the filaments on a rotating mandrel by electrostatic force to form a porous polyurethane tubing having an internal diameter of 10mm ("A compliant small diameter arterial prosthesis," CRC press, 1987; "The design of a small diameter arterial replacement," in Polymers in medicine: Biomedical and pharmacological applications Emo Chiellini & Paolo Giusti Eds, Plenum Press, 1983; "Recent Advances in the development of artificial devices to replace diseased arteries in man: A new elastomeric synthetic artery graft," in Polyurethanes in Biomedical Engineering, Elsevier Science Publishers, 1984; " The design of a small diameter arterial replacement, in Polymers in medicine: Biomedical and Pharmacological Applications Emo Chiellini & Paolo Giusti Eds, Plenum Press, 1983).
The exact components of the above-mentioned "Biomer" polyurethane resins are not known, however, according to Michael D. Lelah, such resins are solvent type polyurethanes synthesized from polytetramethylene glycols having a molecular weight of 2000, 4,4'-diphenylmethanee diisocyanate(MDI), mixture of diamines and silicon compounds (Polyurethane in medicine, CRC press, Inc. 1986).
S. Gogolewski and A. J. Pennings disclose a biodegradable vascular graft prosthesis having an internal diameter of 10 mm and an average pore size of 40-50 .mu.m. The biodegradable vascular graft is prepared by dipping a fluorizated stainless steel mandrel in a mixed resin of a polyurethane resin dissolved in a mixed solvent of DMF and THF and a polyacetide resin dissolved in DMF solvent, followed by placing the coated mandrel in a coagulant consisting of ethanol and water (volume ratio=1:1) ("Compliant, Biodegradable vascular prosthesis" in Polyurethanes in biomedical engineering, Elsevier Science Publishers, 1984).
J. G. F. Bots, L. Van der Does, A. Bantjes disclose a blood vessel prosthesis having pore size of 5-200 .mu.m, which is prepared by forming filaments from a solution of polyethylene oxide, polypropylene oxide and dicumylperoxide, followed by winding the filaments on a rotating mandrel and irradiating them with UV light for 60 minutes. The solvents for dissolving the resins are a mixture solvent of dichloromethane and dichloroethane ("Small diameter blood vessel prostheses from polyethers," in Polymers in medicine II, edited by E. chielline, et al, 1986).
Thomas E. Brothers, James C. Stanley, William e. Burkel and Linda M. Graham disclose a vascular graft. The method for preparing the vascular graft includes forming a polyurethane tubing from a PU resin, B. F. Goodrich Estane 5714 (tradename) to which are added salts, by using the principle of phase inversion, and extracting the salts from the PU resin. The detailed manufacturing procedures are not disclosed ("Small caliber polyurethane and polytetrafluoroethylene grafts: A comparative study in a canine aortoiliac model" Journal of Biomedical Materials Research, vol. 24, pp 761-771, 1990).
Rajagopal R. Kowligi, Wolf W. Von Maltzahn and Robert C. Eberhart disclose a polyurethane tubing fabricated by using the precipitation-flotation method. The method includes premixing polyurethane resin with nitrogen gas in a spray nozzle, spraying the premixture on a flowing water bath in which a rotating mandrel is immersed, causing the polyurethane resin to form into filaments and to coagulate on the water bath and be taken up by the mandrel to form a porous polyurethane tubing. The polyurethane material used is a polyurethane resin with a tradename, "Surethane" and a solid content of 2-5%. The exact components of the polyurethane resin is not disclosed ("Synthetic vascular graft fabrication by a precipitation-floation method," Trans Am Soc Artif Intern Organs, Vol. XXX IV, pp 800-803(1988)).
White et al disclose a microporous polyurethane vascular graft prepared by using replamineform method. The method includes coating a reactive liquid polyurethane resin over a cylindrical mandrel which is formed by mechanically polishing a needlelike protrusion of sea urchin having the composition of calcite, carrying out the polymerization in situ and dipping the mandrel together with the polyurethane tubing formed thereon in a hydrochloride solution to dissolve the mandrel. The resultant polyurethane tubing has an average pore size of 15-20 .mu.m(Michael d. Lelah,"Polyurethane in Medicine", CRC Press, Inc 1986)
Lyman et al also disclose a method of fabricating polyurethane tubing. Their method uses polyurethane resin synthesized from MDI and polypropylene oxide having a molecular weight of 1078 and ethylene diamine. The polyurethane tubing is obtained by using repeated dipping and precipitation method. The precipitating solution used is consisted of water and Dimethyl Formamide(DMF)(Michael d. Lelah, "Polyurethane in Medicine", CRC Press, Inc. 1986) ,
Leidner et al also disclose a method of fabricating porous polyurethane tubings. The method for this fabrication includes extruding polyurethane solution or melt into filaments, stretching the filaments and winding on a rotating mandrel to form a porous tubing(Michael d. Lelah,"Polyurethane in Medicine", CRC Press, Inc 1986)
Kozaburo Hayaski, Tomoyuki Saito et al synthesized a polyurethane resin by using MDI, polytetramethylene glycol(PTMG), polyethylene oxide-polydimethylsiloxanepolyethylene oxide(PES) and ethylene glycol as raw material and reported that a porous polyurethane vascular graft was fabricated. However, the actual procedures and conditions for this fabrication have not been disclosed ("Elastic properties and strength of a novel small-diameter, compliant polyurethane vascular graft," J. Biomed, Mater Res: Applied Biomaterials, vol 123, No. A2, p229-244, 1989).
Shu Qin Lin and Makoto Kodama et al used an aliphatic polyurethane resin, tradename, Tecoflex Sc 80A, having a solid content of 5-10% and solvent 1,4-dioxane, to produce porous polyurethane vascular prostheses. The polyurethane resin is injected into a cavity of a mold, frozen at a temperature of 0.degree. to -196.degree. C. and thawed to obtain a porous polyurethane vascular prosthesis with a pore size form several .mu.m to 70 .mu.m ("Porous polyurethane vascular prostheses with variable compliances", Journal of Biomedical Materials Research, Vol. 26, 1489-1502(1992)).